{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:11:40Z","timestamp":1788459100669,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004732","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000}}],"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI155086"],"award-info":[{"award-number":["R01AI155086"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI155086"],"award-info":[{"award-number":["R01AI155086"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"\nBackground<\/jats:title>\nOral emtricitabine\/tenofovir disoproxil fumarate (F\/TDF) preexposure prophylaxis (PrEP) effectiveness against HIV acquisition highly depends on adherence. For men who have sex with men, a dosing study in the United States (US) population defined clinically meaningful tenofovir diphosphate (TFV-DP) thresholds in dried blood spots (DBS) based on the rounded 25th percentile for 2, 4, and 7 doses\/week as 350, 700, and 1,250\u2009fmol\/punch. However, divergent efficacy results in the first generation randomized clinical trials of F\/TDF PrEP among African women led to several hypotheses to question whether the pharmacology and adherence requirement for oral F\/TDF PrEP may be different in cisgender women compared to what is already established for men.<\/jats:p>\n<\/jats:sec>\n\nMethods and findings<\/jats:title>\nWe conducted an open-label, parallel, randomized directly observed dosing (DOD) study of oral F\/TDF PrEP among women without HIV who were not pregnant or breastfeeding in Kenya. Participants were randomly assigned to 2, 4, or 7 DOD F\/TDF doses\/week for 8 weeks. Blood was collected weekly, and TFV-DP and emtricitabine triphosphate (FTC-TP) concentrations in DBS and peripheral blood mononuclear cells (PBMCs) were quantified using validated liquid chromatography-tandem mass spectrometry. For DBS, concentrations were quantified from a 3-mm punch using the 70% methanol\/30% water (70:30) extraction method as the primary process\u2014the same method used for the original TFV-DP benchmarks derived in US adults, and additionally with 50% methanol\/50% water (50:50) extraction using punches from the same DBS spot to compare the extraction performance of 70:30 versus 50:50 methods. The primary outcome was the steady-state fitted concentrations of TFV-DP and dose proportionality in DBS and the observed PBMC TFV-DP levels by study dosing groups. Secondary outcomes included the quantitative concentrations of FTC-TP in DBS, TFV-DP half-life in DBS, and the relative TFV-DP recovery from DBS using the 70:30 versus 50:50 extraction method. One-compartment population pharmacokinetic models were fit to estimate steady-state DBS concentrations. Descriptive statistics were summarized as range, means, and medians with interquartile range (IQR) for continuous outcomes and proportions for categorical variables.\u00a0Fifty-four women were enrolled and randomized. Median age was 22 (IQR, 20\u201325) years. The observed median (IQR) week 8 TFV-DP concentrations in DBS were 359 (266\u2013464), 749 (596\u2013923), and 1,389 (1,151\u20131,551) fmol\/punch after 2, 4, and 7 doses\/week, respectively. At week 8, FTC-TP was quantifiable in 71%, 19%, and 0% DBS samples for 7, 4, and 2 doses\/week groups, respectively. Fitted median (IQR) steady-state DBS TFV-DP concentrations were 416 (316, 516), 832 (631, 1,033), and 1,457 (1,106, 1,808) fmol\/punch for 2, 4, and 7 doses\/week, respectively, similar to previous estimates in US adults. TFV-DP exhibited a mean half-life of 17.5 days (95%CI: 16.7, 18.4) in DBS and steady-state TFV-DP concentrations varied in direct proportion to the dosing frequency [slope: 1.02 90% confidence interval 0.84, 1.20]. The 50:50 DBS extraction method yielded 1.27 (95% CI 1.25, 1.28) higher TFV-DP concentrations compared to the 70:30 method. When the 1.27 conversion factor was applied to the original 70:30 method-derived TFV-DP thresholds, the updated TFV-DP adherence interpretation benchmarks based on the 50:50 extraction were:\u2009<450 for <2 dose\/week, 450\u2013899 for 2\u20133 doses\/week, 900\u20131,599 for 4\u20136 doses\/week, and \u22651,600\u2009fmol\/punch for 7 doses\/week. The observed mean (standard deviation) steady-state PBMC TFV-DP concentrations was 11.99\u2009\u00b1\u20098.47, 31.81\u2009\u00b1\u200915.66, and 63.1\u2009\u00b1\u200928.97\u2009fmol\/106<\/jats:sup> cells after 2, 4, and 7 doses\/week, respectively. Overall, oral F\/TDF PrEP was well tolerated. No grade 3 or higher adverse events were observed during the dosing phase. The primary study limitation was dosing for 8 weeks, but population pharmacokinetic modeling enabled steady-state estimates.<\/jats:p>\n<\/jats:sec>\n\nConclusions<\/jats:title>\nSteady-state DBS TFV-DP concentrations from directly observed F\/TDF PrEP dosing in African cisgender women participants are similar to previous estimates defined from US-based participants. These data demonstrate that cisgender women achieve similar DBS and PBMC TFV-DP concentrations as men for the same adherence level and validate the original TFV-DP benchmarks to interpret F\/TDF adherence in HIV prevention studies and PrEP programs among cisgender women.<\/jats:p>\n<\/jats:sec>\n\nTrial registration<\/jats:title>\nClinicaltrials.gov: NCT<\/jats:ext-link>05057858<\/jats:ext-link><\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004732","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T17:41:23Z","timestamp":1757439683000},"page":"e1004732","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Adherence thresholds for emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis against HIV acquisition in cisgender women: A randomized directly observed dosing study"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5208-7468","authenticated-orcid":true,"given":"Kenneth K.","family":"Mugwanya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda","family":"Saina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly R.","family":"Mugo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9818-0059","authenticated-orcid":true,"given":"Samantha","family":"MaWhinney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Morrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torin T.","family":"Schaafsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0587-7480","authenticated-orcid":true,"given":"Deborah","family":"Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David V.","family":"Glidden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8062-0933","authenticated-orcid":true,"given":"Kenneth","family":"Ngure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3963-1339","authenticated-orcid":true,"given":"Clare E.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8636-4048","authenticated-orcid":true,"given":"Elena A.","family":"Rechkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2125-6799","authenticated-orcid":true,"given":"Bhavna H.","family":"Chohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7240-5412","authenticated-orcid":true,"given":"Linxuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-2592","authenticated-orcid":true,"given":"Elex","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Koome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6960-3659","authenticated-orcid":true,"given":"Nina","family":"Akelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Mbaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Kibatha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Njeru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9119-3167","authenticated-orcid":true,"given":"Marianne","family":"Muriithi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6430-7444","authenticated-orcid":true,"given":"Corwin","family":"Coppinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lane","family":"Bushman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared M.","family":"Baeten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1200-8494","authenticated-orcid":true,"given":"Peter L.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Women Benchmark Study Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"issue":"5","key":"pmed.1004732.ref001","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1056\/NEJMoa1108524","article-title":"Antiretroviral prophylaxis for HIV prevention in heterosexual men and women","volume":"367","author":"JM Baeten","year":"2012","journal-title":"N Engl J Med"},{"issue":"27","key":"pmed.1004732.ref002","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1056\/NEJMoa1011205","article-title":"Preexposure chemoprophylaxis for HIV prevention in men who have sex with men","volume":"363","author":"RM Grant","year":"2010","journal-title":"N Engl J Med"},{"issue":"7","key":"pmed.1004732.ref003","doi-asserted-by":"crossref","DOI":"10.1097\/QAD.0b013e3283522272","article-title":"Unraveling the divergent results of pre-exposure prophylaxis trials for HIV prevention","volume":"26","author":"A van der Straten","year":"2012","journal-title":"AIDS"},{"issue":"1","key":"pmed.1004732.ref004","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01710-17","article-title":"Intracellular tenofovir-diphosphate and emtricitabine-triphosphate in dried blood spots following directly observed therapy","volume":"62","author":"PL Anderson","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"pmed.1004732.ref005","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S1473-3099(14)70847-3","article-title":"Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study","volume":"14","author":"RM Grant","year":"2014","journal-title":"Lancet Infect Dis"},{"issue":"10246","key":"pmed.1004732.ref006","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0140-6736(20)31065-5","article-title":"Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial","volume":"396","author":"KH Mayer","year":"2020","journal-title":"Lancet"},{"key":"pmed.1004732.ref007","volume-title":"PrEP adherence and effect of drug level feedback among young African women in HPTN 082","author":"C Celum","year":"2019"},{"issue":"13","key":"pmed.1004732.ref008","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1056\/NEJMoa2407001","article-title":"Twice-Yearly lenacapavir or daily F\/TAF for HIV prevention in cisgender women","volume":"391","author":"L-G Bekker","year":"2024","journal-title":"N Engl J Med"},{"issue":"11","key":"pmed.1004732.ref009","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1001\/jama.2024.0464","article-title":"HIV preexposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate among cisgender women","volume":"331","author":"J Marrazzo","year":"2024","journal-title":"JAMA"},{"issue":"151","key":"pmed.1004732.ref010","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3004006","article-title":"Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men","volume":"4","author":"PL Anderson","year":"2012","journal-title":"Sci Transl Med"},{"key":"pmed.1004732.ref011","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3389\/fphar.2019.00401","article-title":"Tenofovir-diphosphate as a marker of HIV pre-exposure prophylaxis use among East African men and women","volume":"10","author":"M Pyra","year":"2019","journal-title":"Front Pharmacol"},{"issue":"112","key":"pmed.1004732.ref012","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3003174","article-title":"Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission","volume":"3","author":"KB Patterson","year":"2011","journal-title":"Sci Transl Med"},{"key":"pmed.1004732.ref013","unstructured":"Kenya Ministry of Health. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection in Kenya 2016. 2018 [cited July 30, 2025]. Available from: https:\/\/www.prepwatch.org\/resources\/guidelines-on-use-of-arv-drugs-for-treating-and-preventing-hiv-infections-in-kenya-2018\/"},{"issue":"20","key":"pmed.1004732.ref014","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.4155\/bio.14.139","article-title":"Adding value to antiretroviral proficiency testing","volume":"6","author":"R DiFrancesco","year":"2014","journal-title":"Bioanalysis"},{"key":"pmed.1004732.ref015","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jpba.2013.08.033","article-title":"Quantitation of tenofovir and emtricitabine in dried blood spots (DBS) with LC-MS\/MS","volume":"88","author":"J-H Zheng","year":"2014","journal-title":"J Pharm Biomed Anal"},{"key":"pmed.1004732.ref016","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jpba.2016.01.038","article-title":"Application of an intracellular assay for determination of tenofovir-diphosphate and emtricitabine-triphosphate from erythrocytes using dried blood spots","volume":"122","author":"J-H Zheng","year":"2016","journal-title":"J Pharm Biomed Anal"},{"issue":"4","key":"pmed.1004732.ref017","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/01.qai.0000225013.53568.69","article-title":"Pharmacogenetic characteristics of indinavir, zidovudine, and lamivudine therapy in HIV-infected adults: a pilot study","volume":"42","author":"PL Anderson","year":"2006","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"7","key":"pmed.1004732.ref018","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciaa1872","article-title":"Tenofovir diphosphate concentrations in dried blood spots from pregnant and postpartum adolescent and young women receiving daily observed pre-exposure prophylaxis in sub-Saharan Africa","volume":"73","author":"L Stranix-Chibanda","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"1","key":"pmed.1004732.ref019","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/pst.241","article-title":"Sample size calculation for the Power Model for dose proportionality studies","volume":"6","author":"VS Sethuraman","year":"2007","journal-title":"Pharm Stat"},{"key":"pmed.1004732.ref020","unstructured":"Division of AIDS (DAIDS). Table for grading the severity of adult and pediatric adverse events, corrected version 2.1. 2017 [cited July 30, 2025]. Available from: https:\/\/rsc.niaid.nih.gov\/sites\/default\/files\/daidsgradingcorrectedv21.pdf"},{"issue":"12","key":"pmed.1004732.ref021","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1097\/QAD.0000000000001145","article-title":"Effectiveness and safety of oral HIV preexposure prophylaxis for all populations","volume":"30","author":"VA Fonner","year":"2016","journal-title":"AIDS"},{"issue":"6","key":"pmed.1004732.ref022","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa1402269","article-title":"Tenofovir-based preexposure prophylaxis for HIV infection among African women","volume":"372","author":"JM Marrazzo","year":"2015","journal-title":"N Engl J Med"},{"issue":"5","key":"pmed.1004732.ref023","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1202614","article-title":"Preexposure prophylaxis for HIV infection among African women","volume":"367","author":"L Van Damme","year":"2012","journal-title":"N Engl J Med"},{"issue":"9","key":"pmed.1004732.ref024","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nri2394","article-title":"The X-files in immunity: sex-based differences predispose immune responses","volume":"8","author":"EN Fish","year":"2008","journal-title":"Nat Rev Immunol"},{"issue":"7","key":"pmed.1004732.ref025","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/infdis\/jis465","article-title":"Innate immune activation enhances hiv acquisition in women, diminishing the effectiveness of tenofovir microbicide gel","volume":"206","author":"V Naranbhai","year":"2012","journal-title":"J Infect Dis"},{"key":"pmed.1004732.ref026","first-page":"74","article-title":"Genital immunology and HIV susceptibility in young women","author":"TJ Yi","year":"2013","journal-title":"Am J Reprod Immunol"},{"issue":"10","key":"pmed.1004732.ref027","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1093\/cid\/ciad021","article-title":"Updating the adherence-response for oral emtricitabine\/tenofovir disoproxil fumarate for human immunodeficiency virus pre-exposure prophylaxis among cisgender women","volume":"76","author":"PL Anderson","year":"2023","journal-title":"Clin Infect Dis"},{"issue":"3","key":"pmed.1004732.ref028","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1097\/QAI.0000000000000172","article-title":"HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention","volume":"66","author":"D Donnell","year":"2014","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"11","key":"pmed.1004732.ref029","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1093\/cid\/ciac313","article-title":"Characterizing HIV-preventive, plasma tenofovir concentrations-a pooled participant-level data analysis from human immunodeficiency virus preexposure prophylaxis clinical trials","volume":"75","author":"M Garcia-Cremades","year":"2022","journal-title":"Clin Infect Dis"},{"issue":"11","key":"pmed.1004732.ref030","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1038\/s41591-023-02564-5","article-title":"Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence","volume":"29","author":"M Moore","year":"2023","journal-title":"Nat Med"},{"issue":"11","key":"pmed.1004732.ref031","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1038\/s41591-023-02615-x","article-title":"Model-based predictions of protective HIV pre-exposure prophylaxis adherence levels in cisgender women","volume":"29","author":"L Zhang","year":"2023","journal-title":"Nat Med"},{"issue":"8","key":"pmed.1004732.ref032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002099","article-title":"Integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1-serodiscordant couples: a prospective implementation study in Kenya and Uganda","volume":"13","author":"JM Baeten","year":"2016","journal-title":"PLoS Med"},{"issue":"6","key":"pmed.1004732.ref033","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1003670","article-title":"PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial","volume":"18","author":"C Celum","year":"2021","journal-title":"PLoS Med"},{"issue":"3","key":"pmed.1004732.ref034","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/QAI.0000000000000974","article-title":"An empiric HIV risk scoring tool to predict HIV-1 acquisition in African women","volume":"72","author":"JE Balkus","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"15","key":"pmed.1004732.ref035","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1097\/QAD.0000000000003062","article-title":"Tenofovir-diphosphate in peripheral blood mononuclear cells during low, medium and high adherence to emtricitabine\/tenofovir alafenamide vs. emtricitabine\/tenofovir disoproxil fumarate","volume":"35","author":"JL Yager","year":"2021","journal-title":"AIDS"}],"updated-by":[{"DOI":"10.1371\/journal.pmed.1004732","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000}}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004732","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:53:33Z","timestamp":1757958813000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004732"}},"subtitle":[],"editor":[{"given":"Marie-Louise","family":"Newell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004732","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pmed.1004732","asserted-by":"object"}]},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,9]]}}}